View of Activity Patch Ethanol Extract Of Leaf Katuk (Sauropus Androgynus L. Merr) 917 1 10 20180427
JURNAL ILMU KEFARMASIAN INDONESIA, April 2018, hlm. 1-5
ISSN 1693-1831
Vol. 16, No. 1
Antiinflammatory Activity Patch Ethanol Extract of Leaf
Katuk (Sauropus Androgynus L. Merr)
(Uji Antiinflamasi Patch Ekstrak Etanol Daun Katuk
(Sauropus androgynus L. Merr))
RISE DESNITA1*, SRI LULIANA1, DESY SISKA ANASTASIA1 AND
MUHAMMAD AKIB YUSWAR1
1
Department of Pharmacy, Faculty of Medicine, Tanjungpura University, Pontianak, 78124,
Indonesia
Diterima 4 Desember 2017, Disetujui 18 Januari 2018
Abstract: The leaf katuk (Sauropus androgynus L. Merr) extract at a dose of 400 mg/kg BW had
antiinflammatory activity in rat by induction of carrageenan. Patch are adhesive plasters containing
medicinal substances placed on the skin to delivery active substances. Patch can offer practicality,
comfort and accuracy of dosage in the application of leaf S. androgynus extract.This research was a
laboratory experimental research by making patch of leaf S. androgynus extract and inflammation effect
used rats as its animal test. Inflammatory healing activity was seen from the percentage reduction in
inflammation in rats after patch application. Patch of leaf S. androgynus extract dose 400 mg/kg BW
has percentage of inflammatory inhibition ranged between 66,67-100%. Statistical test results using
one-way anova patch leaf S. androgynus extract showed good effectiveness in curing inflammation.
Effectiveness between leaf S. androgynus extract patch and diclofenac sodium patch relatively the same
in curing inflammation.
Keywords: patch, antiinflammatory, leaf S. androgynus extract.
Abstrak: Ekstrak daun katuk (Sauropus androgynus L. Merr) dengan dosis 400 mg/kg BB memiliki
aktivitas antiinflamasi pada tikus dengan induksi karagenan. Patch adalah plester perekat yang
mengandung bahan obat yang ditempatkan pada kulit untuk mengirim zat aktif. Patch menawarkan
kepraktisan, kenyamanan dan ketepatan dosis dalam penggunaan ekstrak daun S. androgynus.
Penelitian ini merupakan penelitian eksperimental laboratorium dengan membuat patch ekstrak daun S.
androgynus dan untuk menguji efek inflamasi/peradangan digunakan tikus sebagai hewan uji. Aktivitas
penyembuhan inflamasi terlihat dari persentase pengurangan peradangan pada tikus setelah penggunaan
patch. Patch ekstrak daun S. androgynus dengan dosis 400 mg/kg BB memiliki persentase penghambatan
peradangan berkisar antara 66,67-100%. Hasil uji statistik menggunakan one-way anova, patch ekstrak
daun S. androgynus menunjukkan efektivitas yang baik dalam menyembuhkan peradangan. Efektivitas
antara patch ekstrak daun S. androgynus dan natrium diklofenak relatif sama dalam menyembuhkan
peradangan.
Kata kunci: patch, antiinflamasi, ekstrak daun S. androgynus.
* Correspondence Author, Hp : 08115733100
Email: risedesnita@ymail.com
2 DESNITA ET AL.
INTRODUCTION
UTILIZATION of natural resources as an alternative
in treatment is very rapidly developed today. One
Indonesian native plants used as traditional medicine
in inflammatory is leaf katuk (Sauropus androgynus
L. Merr). Leaf katuk (S. androgynus) significantly
decrease inflammation in rat with dose 100 mg/kg
BW compared with papaverin and morphine. Leaf
S. androgynus ethanol extract at doses of 400 mg/
kg BW had antiinflammatory activity in rat with
carrageenan inducers (1). The leaves of the katuk
are also reported to increase milk production in
rats(2). In addition Kustifah, reported that katuk leaf
extract production of breast milk without degrading
its quality(3). The leaves of katuk have chemicals
such as sterols, resins, tannins, saponins, alkaloids,
flavonoids, terpenoids, cardiac glycosides, phenols,
and catechols(4). Phytochemical leaf screening results
contain polyphenols, anthocyanins, carotenoids,
vitamin C and tannins(5).
Bender and Ismail reported that in 100 g of fresh
katuk leaves contained 580 mg of papaverine alkoxide
compound(6). The extract of S. androgynus leaf is
very potential when given topically it is necessary to
develop a delivery system that can offer practicality,
comfort and accuracy of dose in the application
of leaf extract of S. androgynus. The delivery
system considered in accordance with the criteria is
patch. Patch is adhesive plaster contains medicinal
ingredients placed on the skin to deliver the active
substance. Patch preparations can be occlusive so as
to enhance the hydration and permeability of the skin,
thus facilitating the process of absorption of the active
substance. By making the extract of S. androgynus
leaf in the form of patch is expected to increase antiinflammatory capability and comfort in the use of S.
androgynus leaf extract.
MATERIAL AND METHODS
MATERIAL. Leaf of katuk (Sauropus androgynus
L. Merr), aquadest, 96% technical ethanol, acetic
acid (CH3COOH) glacial (Merck), concentrated
hydrochloric acid (Merck), concentrated sulfuric acid
(H2SO4) (Merck), iron (III ) chloride (FeCl3) 5%
(Merck), chloroform (CH3Cl) (Merck), 0.9% sodium
chloride (NaCl), major reagents, molisch reagents,
dragendorf reagent, spiritus, Hydroxy Propyl Methyl
Cellulose (HPMC Lawsim Zecha), Oppanol B100polyisobutylene (BASF Indonesia), Methyl Paraben,
propylene glycol, glycerin, aquades, 70% ethanol
(Ikapharmindo), alcohol swab (Metz), diclofenac
sodium (Kimia Farma) and lambda carrageenan
Jurnal Ilmu Kefarmasian Indonesia
(Sigma Aldrich).
METHODS. Simplicia Extraction. Fresh leafy
fresh simplicia (Sauropus androgynus L. Merr)
was extracted with 96% ethanol solvent maceration
at room temperature. The extract obtained was
evaporated with a vacuum rotary evaporator and keep
at 40 °C. The extract was then evaporated above the
water bath at 60 °C.
Formulation Gel. The gel preparation formula in
this study refers and is the result of the reformulation
of the Pandit, V., et al7. Gel leaf S. androgynous extract
was prepared by dissolving leaf S. androgynous extract
using aquadest then added ethanol and propylene
glycol. The solution was stirred with 1000 rpm stirrers
for 15 minutes until completely dissolved. Methyl
paraben was dissolved in aquadest then added to gel
mass while stirring with strirrer 800 rpm for 5 min.
The HPMC is dispersed in water while stirring with a
stirrer of 800 rpm for 15 minutes to form a gel mass.
The formed gel is allowed to stand for 12 hours until
the foam disappears and the gel is clear.
Preparation of Patch (Solvent Casting
Technique). The gel mass of 3 grams was poured
into a Petri dish with a diameter of 6 cm then dried
in a 50 °C oven for 3 hours. After drying, 2.5%
polyisobutylene (in n-hexane) solution is poured
over 0.8 gram into the formed film. The drying of the
dosage was continued in a 50 °C oven for 8 minutes.
The formed film is removed from the petri dish
and inserted into aluminum foil and sealed plastic
container and then stored in the desiccator until it is
used.
Evaluation of Patch Weight Uniformity. Picked
3 patches weighed with digital scales. The mean
weight and standard deviation are determined.
Patch Thickness Evaluation. The patch thickness
was measured by 6 different points of each patch
(taken 3 patches randomly) using a digital micrometer
and determined the average thickness as well as the
standard deviation.
Mechanical Strength Patch. The mechanical
strength of the patch is described as tensile strength
and% elongation when the film is torn. The mechanical
strength of the patch is tested with an autograph
consisting of two separately charged parts. The part
below is the retained part (not moving), while the
upper part is the moving part. Cut films with a certain
dimension clipped between two parts, then the style
raised gradually until the film is torn.
The percentage of elongation is determined by
recording the length before the patch is torn, the
Vol 16, 2018
percentage of elongation is determined from the
formula below:
Evaluation of Moisture Content. The film
is weighed individually and stored in a desiccator
containing calcium chloride at room temperature for
24 hours. After 24 hours the film should be weighed
and determined the percentage of moisture content.
Test Anti-Inflammatory Effects. The test animal
is fasted 12 hours before the experiment. Male
Wistar rats were divided into 3 groups (each n = 5),
the first group was the control group (without drug
administration), the second group was given leaf S.
androgynous extract patch and the third group was
given the diclofenac sodium patch. for the transdermal
group, patches were applied to the shaved rat skins
in the thigh area. The left leg of the mouse is marked
with ink on the maleous lateral area. The rat’s foot
volume was measured using the Pletismometer tool by
immersing the rat’s foot to the marked extent. Initial
volume of rat feet was measured and inflammatory
induction was performed with 0.05 mL subcutaneous
injection of 2% lambda carrageenan solution in the
sub-plantar part of rat’s foot (8). Transdermal drug
preparations were administered in group rat two and
three, 30 min after induction, while the first group rat
as control (not given the drug preparation). Performed
rat foot volume measurements at 1, 2, 3, 4, 5, 6, 7 and
8 hours after induced carrageenan lambda.
RESULT AND DISCUSSION
The extraction is done by maseration, soaking the
simplicia into the solvent using maseration vessel.
The maseration method is chosen because it is safe for
compounds that are not resistant to high temperatures,
other than that it is easy and uses a simple tool. The
results of phytochemical screening of S. androgynus
extract contain class of phenol, flavonoids, terpenoids
and tannins. This result differs from the results of
previous studies which suggest that S. androgynus
extract contains chemicals such as sterols, resins,
tannins, saponins, alkaloids, flavonoids, terpenoids,
cardiac glycosides, phenols and catechols(4).
The preparation of leaf S. androgynus extract
patch is made by first making gel of leaf S. androgynus
extract. Then the gel is dried to form a film sheet or
film layer. The gelling agent used is Hydroxy Propyl
Methyl Cellulose (HPMC). HPMC was chosen
because it is able to form a flexible film layer and
strong. The HPMC concentration used in the patch
of leaf katuk extract formula was 9%. This number
Jurnal Ilmu Kefarmasian Indonesia 3
was selected after an experimental trial using HPMC
8, 9 and 10%. Whereas when using HPMC 8%, the
resulting gel is somewhat watered, in contrast to
HPMC 9%, the resulting gel is somewhat viscous
but easily poured. While the gel produced from 10%
HPMC is difficult to pour.
Pouring ability is very important in patch making
process. If the gel is too thick and difficult to pour
it will be difficult to be formed into a sheet of film.
In addition to HPMC in patch of leaf S. androgynus
extract also uses other additives such as methyl
paraben as preservative, propylene glycol and glycerin
as plasticizers. Methyl parabens have good activity
over a wide pH range at pH 5-8. However, the methyl
paraben has a low solubility in water so that it needs a
solvent capable of dissolving methyl paraben.
Propylene glycol and glycerin are selected because
they can dissolve the methyl paraben well, can be
mixed with water, and compatible(9). Plasticizer used
is propylene glycol and glycerin (see table 1). In this
research will be seen the influence of plasticizer on
the elasticity and strength of the resulting patch. The
function of the plasticizer is to fill in the empty space
between the polymer molecules so that when hydrated
it will connect between the polymers and facilitate
the occurrence of diffusion and it can also improve
the mechanical properties of the polymer to form a
flexible, fragile and fragile polymer layer(10).
Moisture content may indicate physical stability of
the preparation. Low moisture content (1.55-3.45%) in
the preparation can maintain the physical stability of
the patch as it can prevent dryness and patchiness so
patches are stable and not fragile but very low moisture
content close to zero leads to fragile patches(11). The
patch of leaf S. androgynus extract using propylene
glycol as plasticizer has a moisture content of 1.859 ±
0.167% so classified as having good physical stability.
The patch of leaf S. androgynus extract that uses
glycerin as a plasticizer has a high water content
that is vulnerable to microbial contamination which
causes the patch to have low physical stability. The
optimization result for long drying was obtained that
drying for 2 hours resulted in patch with moisture
content, tensile strength (TS) and% elongation (EB)
Table 1. Gel formula for leaf S.androgynus extract.
4 DESNITA ET AL.
Jurnal Ilmu Kefarmasian Indonesia
Table 2 . Weight, thickness, moisture content, tensile
strength and% elongation leaf S.androgynus
extract patch (n = 3).
of the desired patch which has low water content, high
tensile strength and high % elongation (see Table 2).
A good patch is a flexible, robust and non-fragile
patch that is marked with relatively high TS and EB
values, but patches that have too high TS values will
be brittle and the folding and pulling process can cause
easily torn films for that need additional plasticizer(10).
The addition of plasticizers such as propylene glycol to
the polymer will lead to an increase in the elongation,
strength and flexibility of the patch, but the addition of
plasticizers causes a decrease in tensile strength and
Young’s modulus12. Patches that are soft and weak
have low TS and EB values, hard and fragile patches
have medium and low EB values, soft and strong
patches have medium and high EB values, hard and
strong patches have high TS and EB values(13). The
patch of leaf S. androgynus extract using propylene
glycol as plasticizer yields tensile strength of 1.080 ±
0.248 kg/mm2 and a high elongation percent of 62.903
± 13.183% so that the patch is soft and strong.
While the patch of leaf katuk leaf extract using
glycerine as plasticizer resulted in moderate tensile
strength of 0.858 ± 0.162 kg/mm 2 and a long
elongation length of 30.564 ± 11.045% so the patch
is hard and brittle. From the experimental results, the
formula which has % elongation close to the library
is a patch of leaf S. androgynus extract formula using
a propylene glycol plasticizer. This suggests the use
of propylene glycol as a plasticizer produces a better
patch (see Fig. 1 and 2).
Figure 2. % Elongation leaf S. androgynus extract patch
The leaf S. androgynus extract patch produced
then tested inflammatory healing activity using rat test
animals. The inflammatory healing activity test begins
with a 0.05 mL injection of a 2% lambda carrageenan
solution in rat feet. The test was performed using 3
groups of rat: the first group was the control group
(without drugs), group two, transdermal patch of leaf
S. androgynus extract dose 400 mg/kg BW, the third
group was transdermal patch of diclofenac sodium
dose 4.5 mg/kg BW. In this anti-inflammatory activity
test, it appears that the patch of leaf S. androgynus
extract has an inflammatory healing effect.
The patch of leaf S. androgynus extract dose 400
mg/kg BW and diclofenac sodium dose patch 4.5 mg/
kg BW was able to suppress inflammation and differ
significantly to control (without drug delivery) at 0,5
to 3 hours with percentage of inflammatory inhibition
ranged between 66.67% -100% for patch of leaf S.
androgynus extract and 44.44% -100% for diclofenac
sodium patch, shown in Fig. 3.
Figure 3. Graph of inflammatory inhibition in
transdermal patch of leaf S. androgynus extract ( , n=5),
transdermal patch group of diclofenac sodium ( , n=5)
Figure 1. Tensile strength (Kg/mm2) leaf
S. androgynus extract patch.
The statistical test using one way anova test showed
that between the AUC the inflammatory percent curve
between the control group was significantly different
from the transdermal patch of leaf S. androgynus
extract and the diclofenac sodium patch (p 0.05) so
that the effectiveness between the leaf S. androgynus
extract patch and the diclofenac sodium patch were
relatively similar in curing inflammation.
CONCLUSION
The leaf S. androgynus extract patch using propylene
glycol as plasticizer had classified as having good
physical stability. The leaf S. androgynus extract patch
dose 400 mg/kg BW has percentage of inflammatory
inhibition ranged between 66,67-100%. Statistical
test results using one-way anova patch leaf S.
androgynus extract showed good effectiveness in
curing inflammation. Effectiveness between leaf
S. androgynus extract patch and diclofenac sodium
patch relatively the same in curing inflammation.
ACKNOWLEDGEMENT
The authors are grateful to all those who have
assisted in this research and the Medical Faculty
of Tanjungpura University for their support.
REFERENCES
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Selvi V, Senthamarai and Baskar A. Characterization of
anti-inflammatory activities and antinociceptive effects
of papaverine from Sauropus androgynus (L.) Merr.,
Global Journal of Pharmacology. 2012. 6(3):186-92.
Saroni T, Sadjimin M, Sja’bani and Zulaela.
Effectiveness of the Sauropus androgynus (L.) Merr
leaf extracts in increasing mother’s breast milk
production. Media Litbang Kes. 2004. 14:20-4.
Kustifah D. Effect of katuk leaves (Sauropus
androgynus Merr.) infusion on the milk production
of mice. In: Widowati., Medicinal Plant Research
from Universities in Indonesia VI. 1st Edition. Jakarta:
Ministry of Health Republic of Indonesia; 1991.159.
Selvi V, Senthamarai and Baskar A. Evaluation of
bioactive components and antioxidant activity of
Sauropus androgynus plant extracts using GC-MS
analysis. International Journal of Pharmaceutical
Sciences Review and Research. 2012. 12(2):65–7.
S Singh, D R Singh, K M Salim, A Srivastava, L B
Singh, and R C Srivastava. Estimation of proximate
composition, micronutrients and phytochemical
compounds in traditional vegetables from Andaman
and Nicobar Islands. International Journal of Food
Sciences and Nutrition. 2011. 62(7):765–73.
Bender A E and K S Ismail. Nutritive value and toxicity
of Sauropus androgynous. The Proceedings of the
Nutrition Society, 1973: 32(2):79A–80A.
Pandit V, Aisha K, Shyamala B, & Vasiha B.
Formulation and evaluation of transdermal films for the
treatment of overactive bladder. International Journal
of Pharma Tech Reasearch. 2009. 1(3):799-804.
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13.
Vogel H G. Drug discovery and evaluation, Germany:
Springer-Verlag Berlin Heidelberg; 2002. 398.
Rowe R C, J S Paul, and E Q Marian. Handbook
of pharmaceutical excipients. 6 th ed. London:
Pharmaceutical Press; 2009. 525-9.
Gal A dan Nussinovitch A. Plasticizers in the
manufacture of novel skin bioadhesive patches. Int
Journal Pharm. 2009:103-9.
Mutalik and Udupa. Glibenclamide transdermal
patches: physicochemical, pharmacodynamic, and
pharmacokinetic evaluations. J Pharm Sci. 2004. 6.
577-94.
Harper C A. Handbook of plastic technologies, the
complete guide to properties and performance. New
York: Mc Graw-Hill Handbooks. 2006.
Aulton M E, Abdul Razzak M H, and Hogan J E. The
mechanical properties of hydroxypropylmethylcellulose
films derived from aqueous system : the influence of
solid inclusions. Drug Dev Ind Pharm. 1981. 7:649-68.
ISSN 1693-1831
Vol. 16, No. 1
Antiinflammatory Activity Patch Ethanol Extract of Leaf
Katuk (Sauropus Androgynus L. Merr)
(Uji Antiinflamasi Patch Ekstrak Etanol Daun Katuk
(Sauropus androgynus L. Merr))
RISE DESNITA1*, SRI LULIANA1, DESY SISKA ANASTASIA1 AND
MUHAMMAD AKIB YUSWAR1
1
Department of Pharmacy, Faculty of Medicine, Tanjungpura University, Pontianak, 78124,
Indonesia
Diterima 4 Desember 2017, Disetujui 18 Januari 2018
Abstract: The leaf katuk (Sauropus androgynus L. Merr) extract at a dose of 400 mg/kg BW had
antiinflammatory activity in rat by induction of carrageenan. Patch are adhesive plasters containing
medicinal substances placed on the skin to delivery active substances. Patch can offer practicality,
comfort and accuracy of dosage in the application of leaf S. androgynus extract.This research was a
laboratory experimental research by making patch of leaf S. androgynus extract and inflammation effect
used rats as its animal test. Inflammatory healing activity was seen from the percentage reduction in
inflammation in rats after patch application. Patch of leaf S. androgynus extract dose 400 mg/kg BW
has percentage of inflammatory inhibition ranged between 66,67-100%. Statistical test results using
one-way anova patch leaf S. androgynus extract showed good effectiveness in curing inflammation.
Effectiveness between leaf S. androgynus extract patch and diclofenac sodium patch relatively the same
in curing inflammation.
Keywords: patch, antiinflammatory, leaf S. androgynus extract.
Abstrak: Ekstrak daun katuk (Sauropus androgynus L. Merr) dengan dosis 400 mg/kg BB memiliki
aktivitas antiinflamasi pada tikus dengan induksi karagenan. Patch adalah plester perekat yang
mengandung bahan obat yang ditempatkan pada kulit untuk mengirim zat aktif. Patch menawarkan
kepraktisan, kenyamanan dan ketepatan dosis dalam penggunaan ekstrak daun S. androgynus.
Penelitian ini merupakan penelitian eksperimental laboratorium dengan membuat patch ekstrak daun S.
androgynus dan untuk menguji efek inflamasi/peradangan digunakan tikus sebagai hewan uji. Aktivitas
penyembuhan inflamasi terlihat dari persentase pengurangan peradangan pada tikus setelah penggunaan
patch. Patch ekstrak daun S. androgynus dengan dosis 400 mg/kg BB memiliki persentase penghambatan
peradangan berkisar antara 66,67-100%. Hasil uji statistik menggunakan one-way anova, patch ekstrak
daun S. androgynus menunjukkan efektivitas yang baik dalam menyembuhkan peradangan. Efektivitas
antara patch ekstrak daun S. androgynus dan natrium diklofenak relatif sama dalam menyembuhkan
peradangan.
Kata kunci: patch, antiinflamasi, ekstrak daun S. androgynus.
* Correspondence Author, Hp : 08115733100
Email: risedesnita@ymail.com
2 DESNITA ET AL.
INTRODUCTION
UTILIZATION of natural resources as an alternative
in treatment is very rapidly developed today. One
Indonesian native plants used as traditional medicine
in inflammatory is leaf katuk (Sauropus androgynus
L. Merr). Leaf katuk (S. androgynus) significantly
decrease inflammation in rat with dose 100 mg/kg
BW compared with papaverin and morphine. Leaf
S. androgynus ethanol extract at doses of 400 mg/
kg BW had antiinflammatory activity in rat with
carrageenan inducers (1). The leaves of the katuk
are also reported to increase milk production in
rats(2). In addition Kustifah, reported that katuk leaf
extract production of breast milk without degrading
its quality(3). The leaves of katuk have chemicals
such as sterols, resins, tannins, saponins, alkaloids,
flavonoids, terpenoids, cardiac glycosides, phenols,
and catechols(4). Phytochemical leaf screening results
contain polyphenols, anthocyanins, carotenoids,
vitamin C and tannins(5).
Bender and Ismail reported that in 100 g of fresh
katuk leaves contained 580 mg of papaverine alkoxide
compound(6). The extract of S. androgynus leaf is
very potential when given topically it is necessary to
develop a delivery system that can offer practicality,
comfort and accuracy of dose in the application
of leaf extract of S. androgynus. The delivery
system considered in accordance with the criteria is
patch. Patch is adhesive plaster contains medicinal
ingredients placed on the skin to deliver the active
substance. Patch preparations can be occlusive so as
to enhance the hydration and permeability of the skin,
thus facilitating the process of absorption of the active
substance. By making the extract of S. androgynus
leaf in the form of patch is expected to increase antiinflammatory capability and comfort in the use of S.
androgynus leaf extract.
MATERIAL AND METHODS
MATERIAL. Leaf of katuk (Sauropus androgynus
L. Merr), aquadest, 96% technical ethanol, acetic
acid (CH3COOH) glacial (Merck), concentrated
hydrochloric acid (Merck), concentrated sulfuric acid
(H2SO4) (Merck), iron (III ) chloride (FeCl3) 5%
(Merck), chloroform (CH3Cl) (Merck), 0.9% sodium
chloride (NaCl), major reagents, molisch reagents,
dragendorf reagent, spiritus, Hydroxy Propyl Methyl
Cellulose (HPMC Lawsim Zecha), Oppanol B100polyisobutylene (BASF Indonesia), Methyl Paraben,
propylene glycol, glycerin, aquades, 70% ethanol
(Ikapharmindo), alcohol swab (Metz), diclofenac
sodium (Kimia Farma) and lambda carrageenan
Jurnal Ilmu Kefarmasian Indonesia
(Sigma Aldrich).
METHODS. Simplicia Extraction. Fresh leafy
fresh simplicia (Sauropus androgynus L. Merr)
was extracted with 96% ethanol solvent maceration
at room temperature. The extract obtained was
evaporated with a vacuum rotary evaporator and keep
at 40 °C. The extract was then evaporated above the
water bath at 60 °C.
Formulation Gel. The gel preparation formula in
this study refers and is the result of the reformulation
of the Pandit, V., et al7. Gel leaf S. androgynous extract
was prepared by dissolving leaf S. androgynous extract
using aquadest then added ethanol and propylene
glycol. The solution was stirred with 1000 rpm stirrers
for 15 minutes until completely dissolved. Methyl
paraben was dissolved in aquadest then added to gel
mass while stirring with strirrer 800 rpm for 5 min.
The HPMC is dispersed in water while stirring with a
stirrer of 800 rpm for 15 minutes to form a gel mass.
The formed gel is allowed to stand for 12 hours until
the foam disappears and the gel is clear.
Preparation of Patch (Solvent Casting
Technique). The gel mass of 3 grams was poured
into a Petri dish with a diameter of 6 cm then dried
in a 50 °C oven for 3 hours. After drying, 2.5%
polyisobutylene (in n-hexane) solution is poured
over 0.8 gram into the formed film. The drying of the
dosage was continued in a 50 °C oven for 8 minutes.
The formed film is removed from the petri dish
and inserted into aluminum foil and sealed plastic
container and then stored in the desiccator until it is
used.
Evaluation of Patch Weight Uniformity. Picked
3 patches weighed with digital scales. The mean
weight and standard deviation are determined.
Patch Thickness Evaluation. The patch thickness
was measured by 6 different points of each patch
(taken 3 patches randomly) using a digital micrometer
and determined the average thickness as well as the
standard deviation.
Mechanical Strength Patch. The mechanical
strength of the patch is described as tensile strength
and% elongation when the film is torn. The mechanical
strength of the patch is tested with an autograph
consisting of two separately charged parts. The part
below is the retained part (not moving), while the
upper part is the moving part. Cut films with a certain
dimension clipped between two parts, then the style
raised gradually until the film is torn.
The percentage of elongation is determined by
recording the length before the patch is torn, the
Vol 16, 2018
percentage of elongation is determined from the
formula below:
Evaluation of Moisture Content. The film
is weighed individually and stored in a desiccator
containing calcium chloride at room temperature for
24 hours. After 24 hours the film should be weighed
and determined the percentage of moisture content.
Test Anti-Inflammatory Effects. The test animal
is fasted 12 hours before the experiment. Male
Wistar rats were divided into 3 groups (each n = 5),
the first group was the control group (without drug
administration), the second group was given leaf S.
androgynous extract patch and the third group was
given the diclofenac sodium patch. for the transdermal
group, patches were applied to the shaved rat skins
in the thigh area. The left leg of the mouse is marked
with ink on the maleous lateral area. The rat’s foot
volume was measured using the Pletismometer tool by
immersing the rat’s foot to the marked extent. Initial
volume of rat feet was measured and inflammatory
induction was performed with 0.05 mL subcutaneous
injection of 2% lambda carrageenan solution in the
sub-plantar part of rat’s foot (8). Transdermal drug
preparations were administered in group rat two and
three, 30 min after induction, while the first group rat
as control (not given the drug preparation). Performed
rat foot volume measurements at 1, 2, 3, 4, 5, 6, 7 and
8 hours after induced carrageenan lambda.
RESULT AND DISCUSSION
The extraction is done by maseration, soaking the
simplicia into the solvent using maseration vessel.
The maseration method is chosen because it is safe for
compounds that are not resistant to high temperatures,
other than that it is easy and uses a simple tool. The
results of phytochemical screening of S. androgynus
extract contain class of phenol, flavonoids, terpenoids
and tannins. This result differs from the results of
previous studies which suggest that S. androgynus
extract contains chemicals such as sterols, resins,
tannins, saponins, alkaloids, flavonoids, terpenoids,
cardiac glycosides, phenols and catechols(4).
The preparation of leaf S. androgynus extract
patch is made by first making gel of leaf S. androgynus
extract. Then the gel is dried to form a film sheet or
film layer. The gelling agent used is Hydroxy Propyl
Methyl Cellulose (HPMC). HPMC was chosen
because it is able to form a flexible film layer and
strong. The HPMC concentration used in the patch
of leaf katuk extract formula was 9%. This number
Jurnal Ilmu Kefarmasian Indonesia 3
was selected after an experimental trial using HPMC
8, 9 and 10%. Whereas when using HPMC 8%, the
resulting gel is somewhat watered, in contrast to
HPMC 9%, the resulting gel is somewhat viscous
but easily poured. While the gel produced from 10%
HPMC is difficult to pour.
Pouring ability is very important in patch making
process. If the gel is too thick and difficult to pour
it will be difficult to be formed into a sheet of film.
In addition to HPMC in patch of leaf S. androgynus
extract also uses other additives such as methyl
paraben as preservative, propylene glycol and glycerin
as plasticizers. Methyl parabens have good activity
over a wide pH range at pH 5-8. However, the methyl
paraben has a low solubility in water so that it needs a
solvent capable of dissolving methyl paraben.
Propylene glycol and glycerin are selected because
they can dissolve the methyl paraben well, can be
mixed with water, and compatible(9). Plasticizer used
is propylene glycol and glycerin (see table 1). In this
research will be seen the influence of plasticizer on
the elasticity and strength of the resulting patch. The
function of the plasticizer is to fill in the empty space
between the polymer molecules so that when hydrated
it will connect between the polymers and facilitate
the occurrence of diffusion and it can also improve
the mechanical properties of the polymer to form a
flexible, fragile and fragile polymer layer(10).
Moisture content may indicate physical stability of
the preparation. Low moisture content (1.55-3.45%) in
the preparation can maintain the physical stability of
the patch as it can prevent dryness and patchiness so
patches are stable and not fragile but very low moisture
content close to zero leads to fragile patches(11). The
patch of leaf S. androgynus extract using propylene
glycol as plasticizer has a moisture content of 1.859 ±
0.167% so classified as having good physical stability.
The patch of leaf S. androgynus extract that uses
glycerin as a plasticizer has a high water content
that is vulnerable to microbial contamination which
causes the patch to have low physical stability. The
optimization result for long drying was obtained that
drying for 2 hours resulted in patch with moisture
content, tensile strength (TS) and% elongation (EB)
Table 1. Gel formula for leaf S.androgynus extract.
4 DESNITA ET AL.
Jurnal Ilmu Kefarmasian Indonesia
Table 2 . Weight, thickness, moisture content, tensile
strength and% elongation leaf S.androgynus
extract patch (n = 3).
of the desired patch which has low water content, high
tensile strength and high % elongation (see Table 2).
A good patch is a flexible, robust and non-fragile
patch that is marked with relatively high TS and EB
values, but patches that have too high TS values will
be brittle and the folding and pulling process can cause
easily torn films for that need additional plasticizer(10).
The addition of plasticizers such as propylene glycol to
the polymer will lead to an increase in the elongation,
strength and flexibility of the patch, but the addition of
plasticizers causes a decrease in tensile strength and
Young’s modulus12. Patches that are soft and weak
have low TS and EB values, hard and fragile patches
have medium and low EB values, soft and strong
patches have medium and high EB values, hard and
strong patches have high TS and EB values(13). The
patch of leaf S. androgynus extract using propylene
glycol as plasticizer yields tensile strength of 1.080 ±
0.248 kg/mm2 and a high elongation percent of 62.903
± 13.183% so that the patch is soft and strong.
While the patch of leaf katuk leaf extract using
glycerine as plasticizer resulted in moderate tensile
strength of 0.858 ± 0.162 kg/mm 2 and a long
elongation length of 30.564 ± 11.045% so the patch
is hard and brittle. From the experimental results, the
formula which has % elongation close to the library
is a patch of leaf S. androgynus extract formula using
a propylene glycol plasticizer. This suggests the use
of propylene glycol as a plasticizer produces a better
patch (see Fig. 1 and 2).
Figure 2. % Elongation leaf S. androgynus extract patch
The leaf S. androgynus extract patch produced
then tested inflammatory healing activity using rat test
animals. The inflammatory healing activity test begins
with a 0.05 mL injection of a 2% lambda carrageenan
solution in rat feet. The test was performed using 3
groups of rat: the first group was the control group
(without drugs), group two, transdermal patch of leaf
S. androgynus extract dose 400 mg/kg BW, the third
group was transdermal patch of diclofenac sodium
dose 4.5 mg/kg BW. In this anti-inflammatory activity
test, it appears that the patch of leaf S. androgynus
extract has an inflammatory healing effect.
The patch of leaf S. androgynus extract dose 400
mg/kg BW and diclofenac sodium dose patch 4.5 mg/
kg BW was able to suppress inflammation and differ
significantly to control (without drug delivery) at 0,5
to 3 hours with percentage of inflammatory inhibition
ranged between 66.67% -100% for patch of leaf S.
androgynus extract and 44.44% -100% for diclofenac
sodium patch, shown in Fig. 3.
Figure 3. Graph of inflammatory inhibition in
transdermal patch of leaf S. androgynus extract ( , n=5),
transdermal patch group of diclofenac sodium ( , n=5)
Figure 1. Tensile strength (Kg/mm2) leaf
S. androgynus extract patch.
The statistical test using one way anova test showed
that between the AUC the inflammatory percent curve
between the control group was significantly different
from the transdermal patch of leaf S. androgynus
extract and the diclofenac sodium patch (p 0.05) so
that the effectiveness between the leaf S. androgynus
extract patch and the diclofenac sodium patch were
relatively similar in curing inflammation.
CONCLUSION
The leaf S. androgynus extract patch using propylene
glycol as plasticizer had classified as having good
physical stability. The leaf S. androgynus extract patch
dose 400 mg/kg BW has percentage of inflammatory
inhibition ranged between 66,67-100%. Statistical
test results using one-way anova patch leaf S.
androgynus extract showed good effectiveness in
curing inflammation. Effectiveness between leaf
S. androgynus extract patch and diclofenac sodium
patch relatively the same in curing inflammation.
ACKNOWLEDGEMENT
The authors are grateful to all those who have
assisted in this research and the Medical Faculty
of Tanjungpura University for their support.
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